Faculty Bibliography

Glutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P>0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.

BACKGROUND:Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN/METHODS:Prospective cohort study. SETTING & PARTICIPANTS/METHODS:14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS/METHODS:/FVC) at baseline determined with spirometry. OUTCOMES/RESULTS:, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS:/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS/CONCLUSIONS:Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS:Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.

Understanding tobacco- and alcohol-related behavioral patterns is critical for uncovering risk factors and potentially designing targeted social computing intervention systems. Given that we make choices multiple times per day, hourly and daily patterns are critical for better understanding behaviors. Here, we combine natural language processing, machine learning and time series analyses to assess Twitter activity specifically related to alcohol and tobacco consumption and their sub-daily, daily and weekly cycles. Twitter self-reports of alcohol and tobacco use are compared to other data streams available at similar temporal resolution. We assess if discussion of drinking by inferred underage versus legal age people or discussion of use of different types of tobacco products can be differentiated using these temporal patterns. We find that time and frequency domain representations of behaviors on social media can provide meaningful and unique insights, and we discuss the types of behaviors for which the approach may be most useful.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Adiposity in pre- and postnatal life may influence menarcheal age. Existing evidence is primarily cross-sectional, failing to address temporality, for which the role of adiposity in early life remains unclear. The current study sought to systematically review longitudinal studies evaluating the associations between birth weight and infant/childhood weight status/weight gain in relation to menarcheal age. METHODS:PubMed, EMBASE, Web of Science, Global Health (Ovid) and CINAHL were systematically searched. Selected studies were limited to English-language articles presenting multi-variable analyses. Seventeen studies reporting risk estimates for birth weight (n = 3), infant/childhood weight gain/weight status (n = 4) or both (n = 10), in relation to menarcheal age were included. RESULTS:Lower vs. higher birth weight was associated with earlier menarche in nine studies and later menarche in one study, while three studies reported a null association. Greater BMI or weight gain over time and greater childhood weight were significantly associated with earlier menarche in nine of nine and six of seven studies, respectively. CONCLUSIONS:Studies suggested that lower birth weight and higher body weight and weight gain in infancy and childhood may increase the risk of early menarche. The pre- and postnatal period may thus be an opportune time for weight control interventions to prevent early menarche, and its subsequent consequences.

BACKGROUND: Due to the increasing prevalence of cannabis use disorder (CUD), the impact of cannabis use on public health may be significant. OBJECTIVE: The present study seeks the possible precursors (e.g., alcohol use) of CUD in order to minimize the potential negative consequences of CUD such as impaired coordination and performance. METHOD: The Harlem Longitudinal Development Study included 674 participants (53% African Americans, 47% Puerto Ricans), with 60% females (n=405) from a six wave survey. We used a growth mixture model to obtain the trajectories of alcohol use from the mean ages of 14 to 36. To examine the associations between alcohol use trajectories and CUD, we used logistic regression analyses with the indicator of CUD as the dependent variable and the indicator of membership in each trajectory group as the independent variables. RESULTS: A three alcohol use trajectory group model was selected. Male gender, higher frequency of cannabis use in adolescence, and a lower educational level were associated with an increased likelihood of having CUD. Membership in the increasing alcohol use group (OR=27.44, p < .01; AOR=15.54, p < .01) and the moderate alcohol use group (OR=10.40, p < .05; AOR=8.63, p < .05) were associated with an increased likelihood of having CUD compared with the membership in the no or low alcohol use group. CONCLUSIONS: The findings of our study support the hypothesis that addressing alcohol use at an early age could impact later CUD.

Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000-2004; n=3538). We defined incident CKD as eGFR<60 ml/min per 1.73 m² and ≥30% eGFR decline at the third visit (2009-2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m² At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m² Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; P

A quarter of people living with human immunodeficiency virus (HIV) infection in the United States are women. Furthermore, African American and Hispanic/Latina women continue to be disproportionately affected by HIV, compared with women of other races/ethnicities. Cannabis use prior to intercourse may be associated with increased risky sexual behaviors which are highly related to HIV. The ultimate goal of this research is to better understand the relationships between unconventional personal attributes (e.g., risk-taking behaviors) in the late 20s, substance use (e.g., alcohol) in the mid 30s, and cannabis use prior to intercourse in the late 30s using a community sample; such an understanding may inform interventions. This study employing data from the Harlem Longitudinal Development Study includes 343 female participants (50% African Americans, 50% Puerto Ricans). Structural equation modeling indicated that unconventional personal attributes in the late 20s were associated with substance use in the mid 30s (beta=0.32, p<0.001), which in turn, was associated with cannabis use prior to sexual intercourse in the late 30s (beta=0.64, p<0.001). Unconventional personal attributes in the late 20s were also directly related to cannabis use prior to sexual intercourse in the late 30s (beta=0.39, p<0.01). The findings of this study suggest that interventions focused on decreasing unconventional personal attributes as well as substance use may reduce sexual risk behaviors among urban African American and Puerto Rican women. Also, the implications of this study for health care providers and researchers working in HIV prevention are that these precursors may be useful as patient screening tools.

OBJECTIVES: This study aimed to evaluate the acceptability of smartphone-based text message- and voice-based ecological momentary assessment (EMA) methods among a sample of low-income housing residents in New York City. Using data from the community-based NYC Low Income Housing, Neighborhoods and Health Study (n = 112), the acceptability of text message- and voice-based EMA methods were assessed via survey. RESULTS: Overall, 88.4% of participants reported that they would participate in a study that utilized text message-based EMA. These analyses showed no appreciable differences by sub-groups (p > .05). Overall, 80.2% of participants reported that they would participate in a study that used voice-based EMA. This voice-based method was least acceptable among participants younger than 25 years old compared to participants of all other ages, chi2(2) = 10.107, p = .006 (among the younger participants 60.7% reported "yes" regarding the anticipated acceptability of voice-based EMA and 39.3% reported "no"). Overall, this work suggests that text message- and voice-based EMA methods are acceptable for use among low-income housing residents. However, the association between age and the acceptability of voice-based EMA suggests that these methods may be less suited for younger populations.

BACKGROUND: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. METHODS: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. RESULTS: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99-1.17)), or with any of the examined subgroups. CONCLUSIONS: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.British Journal of Cancer advance online publication 5 September 2017; doi:10.1038/bjc.2017.299 www.bjcancer.com.

The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5-10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury-a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide.